A variety of naturally occurring steroids, and a number of the compounds of the vitamin D series possess side chains with chiral centers at carbon 24 and/or carbon 25. For example, many plant sterols have alkyl substituents (generally methyl or ethyl) at carbon 24, rendering that carbon a chiral center having either the (R)- or (S)-stereochemical configuration. Similarly, various biologically active and medically useful compounds of the vitamin D series feature a methyl or hydroxy substituent at carbon 24, thereby conferring chirality to that center. For example, the known vitamin D.sub.2 metabolites, 25-hydroxyvitamin D.sub.2 and 1.alpha.,25-dihydroxyvitamin D.sub.2, both feature a methyl substituent at carbon 24, and in these compounds that center has the (24S)-configuration. The corresponding (24R)-epimers of these metabolites, wherein the methyl substituent has the opposite orientation, have also been prepared by chemical synthesis. Likewise, vitamin D metabolites or analogues are known containing a chiral center at carbon 25--such as, for example, 25,26-dihydroxyvitamin D.sub.3, or 1,25-dihydroxy-26-homovitamin D.sub.3 (U.S. Pat. No. 4,717,721).
It is known that the exact stereochemistry of side chain substituents can have a profound effect on the biological properties of steroids and specifically of vitamin D compounds. Hence, in cases where two stereoisomers are possible, it is generally desirable to prepare specifically one or the other of the two, but not a mixture of both. For the case steroid and vitamin D side chain construction, the specific synthesis of one stereoisomer in preference to the other often requires quite elaborate chemical procedures designed to assure the selective formation of one epimer, or else requires the use of laborious and inefficient separation procedures when both stereoisomers are formed in a given reaction sequence.
One of the known methods for the construction of side chains in steroid or vitamin D compounds [e.g. Kutner et al., J. Org. Chem. 53, 3450 (1988)] comprises the condensation of an aryl sulfonyl derivative of the type, ArSO.sub.2 CH.sub.2 R (where Ar signifies an aryl group, and CH.sub.2 R is an alkyl or substituted alkyl group as more fully defined below) with a steroid or vitamin D-22-aldehyde, as illustrated by the transformation below: ##STR1## where N is the steroid or vitamin D nucleus. Similarly, condensation of the same sulfone with a steroid or vitamin D-22-tosylate gives the corresponding saturated side chain structure according to the reaction: ##STR2##
It is readily apparent that by variations in the structure of the CH.sub.2 R unit, a large range of different side chains may be constructed by means of the above condensation processes. It is also apparent that if the desired steroid or vitamin D side chain is to contain a chiral center within R (as, for example, at carbon 24 or 25), having a specific stereochemical orientation (i.e. (R) or (S), but not both), then the use of an optically active ArSO.sub.2 CH.sub.2 R reactant in the above-illustrated condensation process, having a chiral center with that desired stereochemical orientation in the R-moiety would be highly advantageous. The alternative, namely the use of a racemic ArSO.sub.2 CH.sub.2 R reactant (i.e. one in which the chiral center within R is present in both the (R)- and (S)-configuration) would lead to the formation of two epimers of the final steroid or vitamin D product, whose separation may be very difficult and laborious, or impossible by current methods. Hence, in cases where only one chiral form of a side chain is desired, the efficient use of synthons of the type ArSO.sub.2 CH.sub. 2 R for side chain construction according to the above-indicated processes, requires the preparation of these sulfonyl synthons in optically active forms--i.e. as the pure (R) or (S)-epimers, but not a mixture of both.
In previous work certain phenylalkylsulfonyl derivatives have been prepared in optically active form, but these preparations involved elaborate and multistep procedures [Mori et al., Tetrahedron 38, 2099 (1982); Sakahabara et al., Heterocycles 17, 301 (1982); Ferraboschi and Santaniello, Synth. Commun. 14, 1199 (1984); Kociensky et al., J. Chem. Soc. Perkin Trans. 1, 834 (1978); Masamune et al., J. Am. Chem. Soc. 107, 4549 (1985)].
Thus, in view of the practical medical importance of specific steroid side chain stereoisomers--especially in the vitamin D series--there exists a need for methods providing for the convenient preparation of appropriate side chain units in optically active form.